Principal Investigators for Small Business: DiscoveryBioMed, Inc. (DBM) and Monell Chemical Senses Center Project Summary Abstract Bitter taste in foods and medicines presents a barrier to overcoming global public health challenges: food insecurity, poor nutritional health, and poor compliance with medication use, particularly among children and the elderly. Sugar and salt, the mainstays to address these challenges, further erode nutritional health, and current alternatives have adverse taste attributes of their own. We propose to develop a reliable, human taste- cell screening platform to find bitter blockers of commercial interest to the food, flavor, and pharmaceutical industries, with the aim to improve the taste and acceptance of nutritious and sustainable foods and medicines. This Phase 1 STTR proposal has the following goals: (a) to establish immortal human taste-bud-derived epithelial cell cultures and lines (i.e., hTBEC platforms) from donors with bitter-sensitive genotypes and (b) to design, optimize, and implement hTBEC-based bioassays of bitter taste receptor function and other key end points to produce readout data for high-throughput screening (HTS). This proposed research is the initial step toward our ultimate goal of executing a full HTS-based campaign to discover and validate bitter taste receptor antagonists from phytochemicals, phytochemical derivatives, and botanical extracts and extract fractions. This commercial-academic collaboration between DiscoveryBioMed, Inc. and Monell Chemical Senses Center brings together expertise in (a) culture of human taste cells, (b) the creation of immortalized cell lines, (c) HTS, and (c) genetics and human sensory analysis. The hypothesis is that hTBEC-platform-based bioassays will provide a more relevant and robust way to identify new bitter antagonists, given the imperfect current methods of overexpressing known taste receptors in heterologous cells. The discovery of bitter taste receptor antagonists that alone or blended will block bitter taste can improve healthy eating by reducing reliance on salt and sugar and can improve compliance by patients taking medicines. Thus, new bitter blockers will improve human health. PHS 398/2590 (Rev. 09/04, re-issued 4/2006) Page Continuation Format Page